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Published in: Clinical Rheumatology 3/2024

Open Access 31-01-2024 | Lupus Nephritis | ORIGINAL ARTICLE

Clinico-serological associations of urinary activated leukocyte cell adhesion molecule in systemic lupus erythematosus and lupus nephritis

Authors: Arwa S. Amer, Samia M. Abdel moneam, Nashwa I. Hashaad, Eman M. Yousef, Dalia M. Abd El-Hassib

Published in: Clinical Rheumatology | Issue 3/2024

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Abstract

Background

Lupus nephritis (LN) is one of the major complications associated with Systemic Lupus Erythematosus (SLE). Activated leukocyte cell adhesion molecule (ALCAM or CD166) is a promising urine biomarker that binds to CD6, a receptor found on lymphocytes. This binding results in T-cell activation, proliferation, and recruitment, which causes tissue inflammation and may explain the pathophysiology of LN.

Aim of work

Investigate the urinary ALCAM level in SLE, study its relationship to disease activity, and clarify the association with LN activity and histopathology.

Patients and methods

A case–control study was performed on 60 patients with SLE and 20 matched controls. The SLE disease activity index (SLEDAI) and the activity of renal disease (rSLEDAI) were evaluated. Renal biopsy and uALCAM levels were also investigated.

Results

Urinary ALCAM levels were higher significantly in active LN patients than inactive LN patients, active and inactive non-LN SLE, and the control group (p < 0.001). The cut-off value for identifying active and inactive LN was above 270 ng/mg (p < 0.001). ALCAM levels were greater in proliferative (class III, IV, and IV/V) than in non-proliferative (class II and V) LN (p < 0.001). ALCAM exhibited high positive correlations with SLEDAI and rSLEDAI (p < 0.001 each) and negative significant correlations with C3 (p < 0.001) and C4 (p = 0.005).

Conclusion

Urinary ALCAM is a sensitive biomarker evaluating LN in SLE patients. Levels above 270 ng/mg can help distinguish between active and inactive LN. ALCAM levels are correlated positively with SLEDAI and rSLEDAI but have a negative correlation with C3 and C4.
Key Points
Urinary ALCAM shows promise as a biomarker for evaluating kidney dysfunction in SLE patients.
It is a non-invasive marker that can differentiate between proliferative and non-proliferative LN.
A urinary ALCAM level above 270 ng/mg can indicate active LN, while lower levels indicate inactive LN.
Urinary ALCAM levels are correlated positively with SLEDAI and rSLEDAI scores but correlated negatively with C3 and C4.
Appendix
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Literature
1.
go back to reference Guo X, Yang X, Li Q, Shen X et al (2021) The microbiota in systemic lupus erythematosus: An update on the potential function of probiotics. Front Pharmacol 12(9759095):1–12 Guo X, Yang X, Li Q, Shen X et al (2021) The microbiota in systemic lupus erythematosus: An update on the potential function of probiotics. Front Pharmacol 12(9759095):1–12
2.
go back to reference Renaudineau Y, Brooks W, Belliere J (2023) Lupus nephritis risk factors and biomarkers: An update. Int J Mol Sci 24(19):14526-14545 Renaudineau Y, Brooks W, Belliere J (2023) Lupus nephritis risk factors and biomarkers: An update. Int J Mol Sci 24(19):14526-14545
3.
go back to reference So BYF, Yap DYH, Chan TM (2021) MicroRNAs in lupus nephritis-role in disease pathogenesis and clinical applications. Int J Mol Sci 4 22(19):37-60 So BYF, Yap DYH, Chan TM (2021) MicroRNAs in lupus nephritis-role in disease pathogenesis and clinical applications. Int J Mol Sci 4 22(19):37-60
5.
go back to reference ZhangT DV, Vanarsa K, Mohan C (2020) Targeted urine proteomics in lupus nephritis—A meta-analysis. Expert Rev Proteom 17(10):767–776CrossRef ZhangT DV, Vanarsa K, Mohan C (2020) Targeted urine proteomics in lupus nephritis—A meta-analysis. Expert Rev Proteom 17(10):767–776CrossRef
6.
go back to reference Lei R, Thai N, Li Y, Mohan C (2023) Analytical validation of urine ALCAM ELISA as a test for lupus nephritis. Expert Rev Mol Diagn 23(8):729–738 Lei R, Thai N, Li Y, Mohan C (2023) Analytical validation of urine ALCAM ELISA as a test for lupus nephritis. Expert Rev Mol Diagn 23(8):729–738
7.
go back to reference Freitas RF, Basto A, Almeida SC, Santos RF et al (2019) Modulation of CD4 T cell function via CD6-targeting. EBioMedicine 1(47):427–435CrossRef Freitas RF, Basto A, Almeida SC, Santos RF et al (2019) Modulation of CD4 T cell function via CD6-targeting. EBioMedicine 1(47):427–435CrossRef
8.
go back to reference Kalunian K, Furie R, Radhakrishnan J, Mathur V et al (2021) Itolizumab, a novel anti-CD6 therapy, in systemic lupus erythematosus patients: Interim safety results from the phase 1b EQUALISE dose-escalation study. Arthritis Rheumatol 73(10):32–72 Kalunian K, Furie R, Radhakrishnan J, Mathur V et al (2021) Itolizumab, a novel anti-CD6 therapy, in systemic lupus erythematosus patients: Interim safety results from the phase 1b EQUALISE dose-escalation study. Arthritis Rheumatol 73(10):32–72
9.
go back to reference Aringer M, Costenbader K, Daikh D, Brinks R et al (2019) European League Against Rheumatism/ American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 71(9):1400–1412CrossRefPubMedPubMedCentral Aringer M, Costenbader K, Daikh D, Brinks R et al (2019) European League Against Rheumatism/ American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol 71(9):1400–1412CrossRefPubMedPubMedCentral
10.
go back to reference Gladman DD, Ibanez D, Urowltz MB (2000) Systemic lupus erythematosus disease activity index. J Rheumatol 29(2):288–291 Gladman DD, Ibanez D, Urowltz MB (2000) Systemic lupus erythematosus disease activity index. J Rheumatol 29(2):288–291
11.
go back to reference Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT et al (2021) Update οn the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis 80(1):14–25CrossRefPubMed Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT et al (2021) Update οn the diagnosis and management of systemic lupus erythematosus. Ann Rheum Dis 80(1):14–25CrossRefPubMed
12.
go back to reference Weening JJ, D’Agati VD, Schwartz MM, Seshan SV et al (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 15(2):241–250CrossRefPubMed Weening JJ, D’Agati VD, Schwartz MM, Seshan SV et al (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 15(2):241–250CrossRefPubMed
13.
go back to reference Petri M, Barr E, Magder LS (2021) Risk of renal failure within 10 or 20 years of systemic lupus erythematosus diagnosis. J Rheumatol 48(2):222–227CrossRefPubMed Petri M, Barr E, Magder LS (2021) Risk of renal failure within 10 or 20 years of systemic lupus erythematosus diagnosis. J Rheumatol 48(2):222–227CrossRefPubMed
14.
go back to reference Neves A, Viveiros L, Venturelli V, Isenberg DA (2023) Promising experimental treatments for lupus nephritis: Key talking points and potential opportunities. Res Rep Urol 15:333–353PubMedPubMedCentral Neves A, Viveiros L, Venturelli V, Isenberg DA (2023) Promising experimental treatments for lupus nephritis: Key talking points and potential opportunities. Res Rep Urol 15:333–353PubMedPubMedCentral
15.
go back to reference Der E, Zhang T, Mok C, Saxena R et al (2019) CD6-ALCAM signaling is upregulated in kidneys with lupus nephritis and is associated with disease activity. Arthritis Rheumatol 71(10):2894–2899 Der E, Zhang T, Mok C, Saxena R et al (2019) CD6-ALCAM signaling is upregulated in kidneys with lupus nephritis and is associated with disease activity. Arthritis Rheumatol 71(10):2894–2899
16.
go back to reference Ding H, Lin C, Cai J, Guo Q et al (2020) Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology. Arthritis Res Ther 22(122):1–9 Ding H, Lin C, Cai J, Guo Q et al (2020) Urinary activated leukocyte cell adhesion molecule as a novel biomarker of lupus nephritis histology. Arthritis Res Ther 22(122):1–9
17.
go back to reference Parodis I, Gokaraju S, Zickert A, Vanarsa K et al (2020) ALCAM, and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus. Rheumatol Oxford Rheumatol 59(528):2237–2249CrossRef Parodis I, Gokaraju S, Zickert A, Vanarsa K et al (2020) ALCAM, and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus. Rheumatol Oxford Rheumatol 59(528):2237–2249CrossRef
18.
go back to reference Lei R, Vu B, Kourentzi K, Soomro S et al (2022) A novel technology for home monitoring of lupus nephritis that tracks the pathogenic urine biomarker ALCAM. Front Immunol 13(1044743):1–14 Lei R, Vu B, Kourentzi K, Soomro S et al (2022) A novel technology for home monitoring of lupus nephritis that tracks the pathogenic urine biomarker ALCAM. Front Immunol 13(1044743):1–14
19.
go back to reference Chalmers SA, Ramachandran RA, Garcia SJ, Der E et al (2022) The CD6/ALCAM pathway promotes lupus nephritis via T cell–mediated responses. J Clin Invest 132(1):34–50CrossRef Chalmers SA, Ramachandran RA, Garcia SJ, Der E et al (2022) The CD6/ALCAM pathway promotes lupus nephritis via T cell–mediated responses. J Clin Invest 132(1):34–50CrossRef
20.
go back to reference Lécuyer MA, Saint-Laurent O, Bourbonnière L et al (2017) Dual role of ALCAM in neuroinflammation and blood-brain barrier homeostasis. Proc Natl Acad Sci USA 114(4):524–533CrossRef Lécuyer MA, Saint-Laurent O, Bourbonnière L et al (2017) Dual role of ALCAM in neuroinflammation and blood-brain barrier homeostasis. Proc Natl Acad Sci USA 114(4):524–533CrossRef
21.
go back to reference Chu D, Schwartz N, Ampudia J, Guthridge J et al (2022) Urine ALCAM is a strong predictor of lupus nephritis. Arthritis Rheumatol 74(suppl 9) Chu D, Schwartz N, Ampudia J, Guthridge J et al (2022) Urine ALCAM is a strong predictor of lupus nephritis. Arthritis Rheumatol 74(suppl 9)
22.
go back to reference Parodis I, Gokaraju S, Zickert A, Zhang T et al (2018) A role of vascular cell adhesion molecule 1 and activated leukocyte cell adhesion molecule in lupus nephritis. Arthritis Rheumatol 70 (suppl 9) Parodis I, Gokaraju S, Zickert A, Zhang T et al (2018) A role of vascular cell adhesion molecule 1 and activated leukocyte cell adhesion molecule in lupus nephritis. Arthritis Rheumatol 70 (suppl 9)
23.
go back to reference Kim JW, Jung JY, Kim HA, Suh CH (2023) Clinical use of activated leukocyte cell adhesion molecule, hemopexin, and peroxiredoxin 6: A potential urine biomarker for korean patients with systemic lupus erythematosus. Ann Rheum Dis 82:1481 Kim JW, Jung JY, Kim HA, Suh CH (2023) Clinical use of activated leukocyte cell adhesion molecule, hemopexin, and peroxiredoxin 6: A potential urine biomarker for korean patients with systemic lupus erythematosus. Ann Rheum Dis 82:1481
24.
go back to reference Stanley S, Vanarsa K, Soliman S, Habazi D et al (2020) Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities. Nat Commun 11(2197):1–13 Stanley S, Vanarsa K, Soliman S, Habazi D et al (2020) Comprehensive aptamer-based screening identifies a spectrum of urinary biomarkers of lupus nephritis across ethnicities. Nat Commun 11(2197):1–13
Metadata
Title
Clinico-serological associations of urinary activated leukocyte cell adhesion molecule in systemic lupus erythematosus and lupus nephritis
Authors
Arwa S. Amer
Samia M. Abdel moneam
Nashwa I. Hashaad
Eman M. Yousef
Dalia M. Abd El-Hassib
Publication date
31-01-2024
Publisher
Springer International Publishing
Published in
Clinical Rheumatology / Issue 3/2024
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-024-06883-x

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